FIL Study on ABVD DD-DI as Upfront Therapy in HL.

Prior treatment

• Prior chemotherapy or radiation therapy
• Human immunodeficiency virus (HIV) positivity or active infectious A, B or C hepatitis. HBsAg-negative patients with anti-HBc antibody and can be enrolled provided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatment with nucleos(t)ide analogs is provided

Other illness

• Known cerebral or meningeal disease (HL or any other etiology)
• Prior history of malignancies unless the patient has been free of the disease for five years. Exceptions include the following: basal cells carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast and prostate cancer with TNM stage of T1a or T1b
• Uncontrolled infectious disease
• Uncompensated diabetes
• Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment.

Lab values

• Nodular Lymphocyte Predominant HL
• Known hypertension (as defined by the updated Guidelines \[76\]), cardiac arrhythmia, conduction abnormalities, ischemic cardiopathy, left ventricular hypertrophy or left ventricular ejection fraction (LVEF) ≤50% at echocardiography.
• Abnormal QTc interval prolonged (\>450 msec in males; \>470 msec in women)

Other

• Ann Arbor stage IIB without extranodal involvement and/or mediastinal bulky
• Pregnant or lactating females
• Diffusion lung capacity for CO (DLCO) and/or forced expiratory volume in the 1st second (FEV1) tests \<50% of predicted not related to impaired respiratory capacity due to airway compression by mediastinal masses or parenchymal lymphoma
• Refusal of adequate contraception

• Histologically confirmed classical HL
• Previously untreated disease
• Age 18-60 years
• Ann Arbor stage IIB with extranodal involvement and/or mediastinal bulk, III and IV (Appendix A)
• At least one target PET-avid bidimensionally assessable lesion
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 (Appendix B)
• Adequate organ and marrow function as defined below: absolute neutrophil count \>1,0 x109/L, platelets \>75 x109/L
• Total bilirubin \<2 mg/dl without a pattern consistent with Gilbert's syndrome
• Aspartate Transaminase and Alanine Transaminase (AST/ALT) \<3 X institutional Upper Limits of Normality (ULN)
• Creatinine within normal institutional limits or creatinine clearance \>50 mL/min/1.72 m2 (Appendix C)
• Females of childbearing must have a negative pregnancy test at medical supervision even if had been using effective contraception
• Life expectancy \> 6 months
• Able to adhere to the study visit schedule and other protocol requirements
• Sign (or their legally acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Access to PET-CT scans facilities qualified by FIL